Giardia duodenalis, Enterocytozoon bieneusi and Cyclospora cayetanensis are usually classified as Neglected Tropical Diseases, causing giardiasis, microsporidiosis and cyclosporiasis, respectively, which significantly contributed to food- and water-transmitted intestinal illnesses in both humans and animals. In this study, we conducted on the prevalence and molecular characterization of Giardia, E. bieneusi and C. cayetanensis of diarrheal outpatients from three areas in the Yangtze River Delta, China. A total of 2 720 fecal samples were collected and nested PCR was used to identify and describe the genetic characteristic of Giardia, E. bieneusi and C. cayetanensis. The overall prevalence of the three pathogens was 2.54

In China, inpatient/outpatient visits for rotavirus (RV)-associated diarrhea are common among children aged < 5 years. An interim analysis evaluated RV genotype circulation in China in an ongoing observational effectiveness study of a pentavalent (RV5) vaccine. Data were collected (October 2020-March 2021) from children eligible for vaccination with three doses of RV5 and receiving treatment for acute gastroenteritis. RV gastroenteritis was reported in 494 (62.1

Selective autophagy of the endoplasmic reticulum (ER-phagy) is critical for ER proteostasis and host defense, yet how ER quality-control pathways interface with ER-phagy to restrict viral glycoproteins remains poorly defined. Previously, the 1st known ER-phagy receptor gene RETREG1 (RETR1)/FAM134B gene was reported to restrict Ebola virus (EBOV) replication in vivo by inhibiting the viral glycoprotein (GP) and viral protein 40 kDa (VP40) expression, but this mechanism remains unknown. Here, we identify the truncated RETR1/FAM134B isoform 2 (RETR1-2), but not its full-length protein RETR1, as an ER-phagy receptor that targets EBOV-GP for degradation. RETR1-2 broadly triggers GP degradation across ebolavirus species but not Marburg virus and inhibits EBOV replication. Mechanistically, RETR1-2 recognizes EBOV-GP via its luminal domain, undergoes GP-induced oligomerization, and directs GP-containing ER membranes to lysosomes through canonical macro-autophagy. Using unbiased mass spectrometry, we identified TOLLIP as the key cytoplasm adaptor for RETR1-2, which also requires cooperation with the ER chaperone calnexin for EBOV-GP degradation. Notably, the PI3P-binding C2 domain of TOLLIP mediates its interaction with RETR1-2, and the EBOV-GP degradation occurs independently of ubiquitination, revealing an unexpected role for TOLLIP in ER-phagy. Furthermore, EBOV-VP40 antagonizes this pathway by selectively targeting RETR1-2 for macroautophagic degradation independently of TOLLIP, thereby restoring GP expression and viral infectivity. Nevertheless, RETR1-2 reciprocally degrades VP40 via a similar mechanism. Together, these findings define a calnexin-TOLLIP-RETR1-2 axis that links ER quality control to ER-phagy-mediated antiviral restriction and uncover a reciprocal host-virus arms race centered on selective macro-autophagy.

Reticulophagy regulator 1 (RETREG1)/Family with sequence similarity 134 member B (FAM134B) is a selective endoplasmic reticulum (ER)-phagy receptor that mediates starvation-induced macro-ER-phagy, but whether it participates in other pathways mediating ER turnover has remained unclear. Here, we unveil a previously unrecognized role for RETREG1 in micro-ER-phagy and show how the murine leukemia virus (MLV) accessory protein glycosylated group-specific antigen (glycoGag) exploits this pathway to antagonize the host restriction factor SERINC5 (serine incorporator 5). GlycoGag binds SERINC5 in the endoplasmic reticulum (ER) and selectively recruits RETREG1 to eliminate SERINC5 through an autophagosome-independent process that bypasses ATG3 (autophagy-related), ATG5, ATG7, BECN1 (Beclin-1), LC3 (microtubule-associated protein 1 light chain 3) lipidation, and PIK3C3 (phosphatidylinositol 3-kinase catalytic subunit type 3)/hVPS34 (vacuolar protein sorting 34). RETREG1 knockout abolishes degradation of ER-retained SERINC5, whereas endolysosomal turnover of surface SERINC5 remains partially intact, demonstrating that glycoGag utilizes dual ER-phagy and endolysosomal routes to suppress SERINC5. These findings expand the functional repertoire of RETREG1 in autophagy, identify that retroviruses repurpose micro-ER-phagy to circumvent SERINC5-mediated restriction, and reveal ER-phagy as an understudied battleground in the ongoing arms race between cellular restriction factors and viral accessory proteins.

Patients with rheumatoid arthritis (RA) are reported to be more vulnerable to coronavirus disease 2019 (COVID-19), so clinical severity is a particular concern for them. This meta-analysis was performed to evaluate the clinical outcomes in RA patients with COVID-19. A systematic literature search was performed in electronic databases for relevant articles published from January 2020 to October 2022. We extracted necessary relevant data and Egger's test was used to evaluate the risk of publication bias. This meta-analysis included 9 studies with a total of 12 339 RA patients with COVID-19 and 685 982 non-RA patients with COVID-19. We found serious adverse outcomes in RA patients with COVID-19, including the rates of severity (OR: 1.59, 95% CI: 1.23-2.05, p = .0004), hospitalization (OR: 1.73, 95% CI: 1.55-1.92, p < .00001), mortality (OR: 1.92, 95% CI: 1.67-2.20, p < .00001), mechanical ventilation (OR: 1.64, 95% CI: 1.47-1.84, p < .00001), despite no significant difference observed in ICU admission (OR: 1.37, 95% CI: 0.95-1.98, p = .09). Our data suggests that RA patients had an increased risk of adverse clinical outcomes with COVID-19 infection.

Foodborne pathogen contamination of fermented food is an increasingly concerned problem in food industry. The types and sources of harmful microorganisms in food are discussed in this paper. The main techniques used to detect microorganisms are summarized. In addition, strategies for controlling these harmful microorganisms are discussed. By highlighting these important aspects, this paper aims to contribute to strengthening food quality assurance and promoting safer food practices.

Motivated by the need to assess consistency in the outcomes of aquatic toxicity tests conducted by different labs at different time points, we propose a clustering of variance method in linear mixed models. The proposed method, referred as CVM, is able to identify the cluster structure of the variances and estimate model parameters simultaneously. In our proposed method, a penalized approach based on pairwise penalties is proposed to identify the cluster structure. We construct an optimization problem and develop an algorithm based on the alternating direction method of multipliers. Simulation studies show that the proposed approach can identify the cluster structure well and outperforms traditional methods based on k-means. In the end, the proposed approach is applied to the aquatic toxicity assessment data, which gives a more reasonable cluster structure than the traditional methods.

The determinants of persistent human papillomavirus (HPV) infection remain largely unknown, and existing studies have predominantly focused on the female population. Individual genetic background may influence the persistence of HPV infection, we the evidence overall and among human immunodeficiency virus (HIV)-positive males are very limited. We conducted a genome-wide association study (GWAS) to identify single nucleotide polymorphisms (SNPs) associated with anal HPV persistence, based on a cohort designed to study the natural history of anal HPV infection among HIV-positive males in Taizhou, China from 2016 to 2022. A total of 322 HIV-positive males with anal HPV infection, with a mean age of 43.0 (standard deviation [SD]: 13.8) years, were included in this GWAS. The median follow-up time was 1.8 (interquartile range [IQR]: 1.5-2.0) years. The persistence of any type of HPV infection was 53.4%. After adjusting for age and sexual orientation, there were 2 SNPs with p < 1 × 10-5 and 24 SNPs with p < 1 × 10-4. The most closely associated with HPV persistence in additive models were rs7359031 (LOC105370461, odds ratio [OR]T/C = 0.36, 95% confidence interval [CI]: 0.24-0.56; p = 6.67 × 10-6) located at 14q21.1, and rs11046048 (PYROXD1, ORC/A = 0.41, 95% CI: 0.28-0.60; p = 7.80 × 10-6) located at 12p12.1. Other SNPs were mainly located at 6q23.3 (HBS1L-MYB) and 6p21.33 (CCHCR1, PSORS1C3). LOC105370461, PYROXD1, HBS1L-MYB, CCHCR1, and PSORS1C3 may be susceptible genes for HPV persistence. We appeal further studies to validate these associations and examine the underlying mechanisms.

Writing centres have become increasingly popular in China’s mainland as an innovative educational site to support second language learners’ writing and publication and to accommodate the internationalisation mission of Chinese higher education. It is therefore important to investigate the identities of new writing centre directors (WCDs)/founders to support the professional development of WCDs and the development of Chinese writing centres, which is barely examined in the existing research. Based on the notions of community of practice (CoP) and identity-in-practice, this paper examined 11 new WCDs/founders' self-perceived identities at different Chinese universities with interviews and photo elicitation methods. Six predominant metaphors of new WCD identities were found: first, administrator, scholar and leader, which aligns with traditional WCD identities documented in North American writing centre literature; and second proofreader, collaborator and “one-person army”, which reflects the distinct localised managerial philosophies of writing centres in the EFL context, pointing to the pragmatic challenges faced by new WCDs in China. This research suggests it is crucial for new WCDs to further develop scholar and leader identities and to form communities of practice within the local writing centre (the local CoP) and across university writing centres (the national CoP) in China’s mainland.

SARS‐CoV‐2 is still spreading globally. Studies have reported the stability of SARS‐CoV‐2 in aerosols and on surfaces under different conditions. However, studies on the stability of SARS‐CoV‐2 and viral nucleic acids on common food and packaging material surfaces are insufficient. The study evaluated the stability of SARS‐CoV‐2 using TCID 50 assays and the persistence of SARS‐CoV‐2 nucleic acids using droplet digital polymerase chain reaction on various food and packaging material surfaces. Viral nucleic acids were stable on food and material surfaces under different conditions. The viability of SARS‐CoV‐2 varied among different surfaces. SARS‐CoV‐2 was inactivated on most food and packaging material surfaces within 1 day at room temperature but was more stable at lower temperatures. Viruses survived for at least 1 week on pork and plastic at 4°C, while no viable viruses were detected on hairtail, orange, or carton after 3 days. There were viable viruses and a slight titer decrease after 8 weeks on pork and plastic, but titers decreased rapidly on hairtail and carton at –20°C. These results highlight the need for targeted preventive and disinfection measures based on different types of foods, packaging materials, and environmental conditions, particularly in the cold‐chain food trade, to combat the ongoing pandemic.

IMPORTANCE In 2022, Omicron variants circulated globally, and Urumqi, China, experienced a COVID-19 outbreak seeded by Omicron BA.5 variants, resulting in the highest number of infections in the city's record before the exit of the zero COVID-19 strategy. Little was known about the characteristics of Omicron variants in mainland China. OBJECTIVE To evaluate transmission characteristics of Omicron BA.5 variants and the effectiveness of inactivated vaccine (mainly BBIBP-CorV) against their transmission. DESIGN, SETTING, AND PARTICIPANTS This cohort study was conducted using data from an Omicron-seeded COVID-19 outbreak in Urumqi from August 7 to September 7, 2022. Participants included all individuals with confirmed SARS-CoV-2 infections and their close contacts identified between August 7 and September 7, 2022 in Urumqi. EXPOSURES A booster dose was compared vs 2 doses (reference level) of inactivated vaccine and risk factors were evaluated. MAIN OUTCOMES AND MEASURES Demographic characteristics, timeline records from exposure to laboratory testing outcomes, contact tracing history, and contact settingwere obtained. The mean and variance of the key time-to-event intervals of transmission were estimated for individuals with known information. Transmission risks and contact patterns were assessed under different diseasecontrol measures and in different contact settings. The effectiveness of inactivated vaccine against the transmission of Omicron BA.5 was estimated using multivariate logistic regression models. RESULTS Among 1139 individuals diagnosed with COVID-19 (630 females [55.3%]; mean [SD] age, 37.4 [19.9] years) and 51 323 close contacts who tested negative for COVID-19 (26 299 females [51.2%]; mean [SD] age, 38.4 [16.0] years), the means of generation interval, viral shedding period, and incubation period were estimated at 2.8 days (95% credible interval [CrI], 2.4-3.5 days), 6.7 days (95% CrI, 6.4-7.1 days), and 5.7 days (95% CrI, 4.8-6.6 days), respectively. Despite contact tracing, intensive control measures, and high vaccine coverage (980 individuals with infections [86.0%] received similar to 2 doses of vaccine), high transmission risks were found in household settings (secondary attack rate, 14.7%; 95% CrI, 13.0%-16.5%) and younger (aged 0-15 years; secondary attack rate, 2.5%; 95% CrI, 1.9%-3.1%) and older age (aged >65 years; secondary attack rate, 2.2%; 95% CrI, 1.5%-3.0%) groups. Vaccine effectiveness against BA.5 variant transmission for the booster-dose vs 2 doses was 28.9%(95% CrI, 7.7%-45.2%) and 48.5%(95% CrI, 23.9%-61.4%) for 15-90 days after booster dose. No protective outcome was detected beyond 90 days after the booster dose. CONCLUSIONS AND RELEVANCE This cohort study revealed key transmission characteristics of SARS-CoV-2 as they evolved, as well as vaccine effectiveness against variants. These findings suggest the importance of continuously evaluating vaccine effectiveness against emerging SARS-CoV-2 variants.

Abstract Reticulophagy reduces Zaire Ebolavirus (EBOV) glycoprotein GP 1,2 expression, and thus increases viral fitness. Reticulophagy degrades endoplasmic reticulum (ER) subdomains containing misfolded proteins to restore the ER proteostasis, but whether degraded cargo proteins are polyubiquitinated is still unknown. Here, we show that the calnexin-calreticulin cycle promoted EBOV-GP 1,2 misfolding via PDIA3/ERp57, and that misfolded GP 1,2 was degraded via reticulophagy dependent on ATG3, ATG5, and SQSTM1/p62. EBOV-GP 1,2 degradation also required its lysine 673 (K673), which served as a substrate for K27-linked ubiquitination. Although E3 ubiquitin ligases RNF26, RNF185, MARCH8, and TRIM25 either degraded or polyubiquitinated EBOV-GP 1,2 , only RNF185 had both activities. Thus, RNF185 polyubiquitinates misfolded EBOV-GP 1,2 in the ER and then SQSTM1/p62 recruits polyubiquitinated GP 1,2 into autophagosomes for autophagic degradation. We conclude that ubiquitin is required for reticulophagy, which has played a major role in other autophagic pathways. In addition, EBOV infection should be blocked by enhanced GP 1,2 degradation via reticulophagy.

Immunological evaluation of an mRNA vaccine booster in individuals fully immunized with an inactivated SARS-CoV-2 vaccineDear Editor, More than 5.75 million deaths and 396.55 million cases of coronavirus disease 2019 (COVID-19) have been reported, including those caused by at least five variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 1This situation has caused public concern about the effectiveness of immune responses to emerging variants elicited by boosters of different vaccines in previously immunized populations. 2,3Our study, based on a cohort immunized with two doses of the inactivated vaccine and boosted with the messenger RNA (mRNA) vaccine at an interval of 6 months, investigates immunity of heterologous vaccination.The inactivated and mRNA vaccines used in this study were developed based upon the sequence of the Wuhan strain. 4,5In total, 288 healthy adult volunteers were immunized with an inactivated vaccine (150 U/dose) at an interval of 14 days; neutralizing antibodies were identified as having a geometric mean titer (GMT) of 2.1 and as negative in 52% of this population at 6 months after full immunization.Among them, 118 and 97 immunized subjects were boosted with the inactivated (150 U/dose) or mRNA (25 μg/dose) vaccine, and 73 immunized subjects were monitored as non-boosted controls.The average ages of the three groups were 43.04 ± 13.05, 31.86 ± 7.62 and 30.05 ± 7.03 years, respectively (Table S1).Immunological observation was until day 180 post-boost, which was available for 60, 61 and 68 subjects in the inactivated vaccine boost, mRNA vaccine boost and nonboosted groups, respectively (Figure S1).Antibody assays performed at days 14 and 180 post-boost showed GMTs of 829 and 455 on days 14 and 180, respectively, against the Wuhan strain in the mRNA boost group, in comparison to GMTs of 39 and 19, respectively, in the inactivated vaccine boost group (Figure 1).Binding antibody titers reached 71864 and 29675 and 3162 and 1993 on days 14 and 180, respectively, in the mRNA and inactivated vaccine boost groups (Figure 1).Further cross-neutralization for the B.1.617.2 and B.1.1.

Intake of radionuclides and heavy metals through food consumption is one of the important pathways for long-term health considerations. In this paper, the dietary exposure to radionuclides ( 210 Pb, 210 Po, 226 Ra, 228 Ra, 40 K, 137 Cs and 129 I) and heavy metals (As, Hg, Pb, Cd and U) of adult residents in the high background natural radiation area (HBNRA) in Yangjiang, China, was comprehensively assessed using duplicate diet method. The estimated effective dose received by the inhabitants in HBNRA from ingestion of radionuclides was 0.33 mSv/y, and the associated lifetime cancer risk was 1.1 × 10 –3 . Both the dose and cancer risk to humans were at the acceptable range, and showed no difference between the HBNRA and the control area. With respect to heavy metals, the estimated daily intake of heavy metals (DIM) values for As, Hg, Pb, Cd and U in HBNRA were 0.47, 0.03, 15.0, 0.26 and 0.04 μg/kg bw/d, respectively, and the corresponding target hazard quotient (THQ) were 1.58, 0.09, 3.7, 2.56, 0.18. The DIM and THQ of Cd and U in HBNRA were similar to the control area, but the DIM and THQ of Pb were much higher than the corresponding values of 0.39 and 0.03 in the control area. The hazard index (HI) value of heavy metals in HBNRA was almost twice that of the control area. This suggests that the inhabitants in the HBNRA may have a health risk associated with the heavy metals.

Virus infection affects cellular proteostasis and provides an opportunity to study this cellular process under perturbation. The proteostasis network in the endoplasmic reticulum (ER) is composed of the calnexin cycle, and the two protein degradation pathways ER-associated protein degradation (ERAD) and ER-to-lysosome-associated degradation (ERLAD/ER-phagy/reticulophagy). Here we show that calnexin and calreticulin trigger Zaire Ebolavirus (EBOV) glycoprotein GP1,2 misfolding. Misfolded EBOV-GP1,2 is targeted by ERAD machinery, but this results in lysosomal instead of proteasomal degradation. Moreover, the ER Ub ligase RNF185, usually associated with ERAD, polyubiquitinates EBOV-GP1,2 on lysine 673 via ubiquitin K27-linkage. Polyubiquinated GP1,2 is subsequently recruited into autophagosomes by the soluble autophagy receptor sequestosome 1 (SQSTM1/p62), in an ATG3- and ATG5-dependent manner. We conclude that EBOV hijacks all three proteostasis mechanisms in the ER to downregulate GP1,2 via polyubiquitination and show that this increases viral fitness. This study identifies linkages among proteostasis network components previously thought to function independently.

Objective::To explore the concentration level of radionuclide in mushrooms in northeast China, and to analyze the risk of the effective dose of edible mushrooms to the human body.Methods::A total of 68 samples of 18 species of mushrooms from three regions in northeast China and Beijing as control were collected from 2017 to 2020. The activity of radionuclide in mushrooms was measured by gamma-spectrometry, and the activity was analyzed by statistical analysis. The relationship between 137Cs and 40K content in mushrooms was explored. Results::238U was undetected in all samples. The activity concentration of 226Ra, 232Th, 40K, 137Cs were in range of 1-34.3, 2.26-32.3, 208-2,388 and 0.6-130.3 Bq/kg, respectively. The 137Cs and 40K concentrations in mushrooms were not correlated. The risk analysis of radioactivity in the collected mushrooms showed that the highest effective dose of the 18 kinds of mushrooms was 0.042 mSv. Conclusion::The radionuclide content of mushrooms in northeast China is within the normal range. The mushrooms will not cause risk to human health.

Objective This study aimed to analyze the clinical manifestation, prognosis, and risk factors of pediatric chronic active Epstein-Barr virus infection (CAEBV) associated with gastrointestinal tract involvement.Methods This retrospective case series study included pediatric CAEBV associated with gastrointestinal tract involvement treated at Beijing Children’s Hospital, Capital Medical University from June 2017 to Jun 2021. The control group was consisted of Children with CAEBV without gastrointestinal involvement. The clinical manifestations, laboratory and ultrasound examinations, treatment and prognosis of the children were observed.Results There were 15 children with CAEBV combined with gastrointestinal involvement, including 11 males and 4 females, accounting for 20.8% (15/72) of CAEBV patients in the same period, with an onset median age of 3.71 (0.64-14.47) years. The most common clinical manifestation at onset was diarrhea (13/15). Gastrointestinal ultrasound showed air accumulation accompanied by intestinal wall swelling and thickening, mild to moderate swelling of the surrounding mesentery and omentum, and enhanced echo. The endoscopic features were hyperemia, edema, and ulcers of variable morphological characteristics. Pathological examination showed lymphocyte infiltration with EBER (+), and the common involvement locations were the colon (n=6) and gastric antrum (n=3). The median follow-up time was 13.26 (0.31-51.89) months. Ten patients survived, and 5 patients died (including one patient who died of intestinal perforation due to necrotizing enterocolitis). Compared with the control group, the case group had higher levels of alanine aminotransferase, aspartate aminotransferase and whole blood EBV-DNA copies (P=0.038, 0.040 and < 0.001) and lower NK cell activity (P < 0.001). The 3-year overall survival rate of the case group was significantly lower than that of the control group (59.3%±12.9% vs. 79.4%±4.9%, P=0.021).Conclusion The incidence of CAEBV with gastrointestinal tract involvement was low. The most common involvement location was colon. CAEBV with gastrointestinal involvement had poor prognosis. Patients who had high whole blood EBV-DNA copy levels early in their illness were more likely to develop gastrointestinal involvement.

Cryptosporidium is a life-threating protozoan parasite belonging to the phylum Apicomplexa, which mainly causes gastroenteritis in a variety of vertebrate hosts. Currently, there is a reemergence of Cryptosporidium infection; however, no fully effective drug or vaccine is available to treat Cryptosporidiosis. In the present study, to better understand the detailed interaction between the host and Cryptosporidium parvum, a large-scale label-free proteomics study was conducted to characterize the changes to the proteome induced by C. parvum infection. Among 4406 proteins identified, 121 proteins were identified as differentially abundant (> 1.5-fold cutoff, P < 0.05) in C. parvum infected HCT-8 cells compared with uninfected cells. Among them, 67 proteins were upregulated, and 54 proteins were downregulated at 36 h post infection. Analysis of the differentially abundant proteins revealed an interferon-centered immune response of the host cells against C. parvum infection and extensive inhibition of metabolism-related enzymes in the host cells caused by infection. Several proteins were further verified using quantitative real-time reverse transcription polymerase chain reaction and western blotting. This systematic analysis of the proteomics of C. parvum-infected HCT-8 cells identified a wide range of functional proteins that participate in host anti-parasite immunity or act as potential targets during infection, providing new insights into the molecular mechanism of C. parvum infection.

Ebola viruses (EBOV) express cytotoxic structural glycoprotein GP1,2 to mediate virus entry. To explore a novel viral fitness mechanism, we used mass spectrometry to investigate how EBOV-GP1,2 expression is regulated in the endoplasmic reticulum (ER). We found that ER protein 57 (ERp57), a member of protein disulfide isomerases (PDIs) that promote protein folding, targets EBOV-GP1,2 cysteine residues required for correct cross-linking, thus adverselytriggering misfolding, which in turn activates the unfolded protein response. Misfolded EBOV-GP1,2 is targeted by ER-associated protein degradation machinery and, unexpectedly, is degraded in lysosomes via autophagosomes, but not proteasomes. Five other PDIs also have similar inhibitory activity. In contrast, the expression of Marburg virus and some other enveloped virus glycoproteins is increased by ERp57. Thus, PDIs can negatively regulate EBOV glycoprotein expression, which enables optimum viral infectivity and minimizes cytotoxicity. Importantly, PDIs emerge as potential targets for inhibition of Ebola virus infection.